Paternal uniparental disomy for chromosome 6 causes transient neonatal diabetes.

Whiteford, Margo; Narendra, A; White, M.P.; Cooke, Alexander; Wilkinson, A G; Robertson, Kenneth; Tolmie, John

doi:10.1136/jmg.34.2.167

Cited by 44 publications

(17 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…10 The association between TNDM and paternal UPD6 has been observed in at least six independent cases in various ethnic groups. 4,5 These recent reports and our observation are in favour of the involvement of imprinted gene(s) on the chromosome region 6q23-q24. 6 Chromosome 6 paternal isodisomy is found in approximately 20-30% of patients with TNDM.…”

Section: Discussionsupporting

confidence: 64%

“…Chromosome 6 duplications, 2,3 and paternal uniparental disomy of chromosome 6 (UPD6), isodisomy, have been described in patients with TNDM. 4,5 A candidate region on 6q23-q24 has been identified with an imprinted gene thought to be involved in the maturation of pancreatic beta-cells. 6 We report two further cases of TNDM with paternal UPD6, with different growth patterns and clinical abnormalities.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Variable features of transient neonatal diabetes mellitus with paternal isodisomy of chromosome 6

et al. 2000

View full text Add to dashboard Cite

We describe two patients who suffered transient neonatal diabetes mellitus (TDNM), due to paternal isodisomy of chromosome 6. One patient, now 5 years old, had severe intra-uterine growth retardation, but recovered normal growth parameters. The other patient, currently 12 years old, had a normal birth weight but showed impaired post-natal growth; in addition to TNDM the patient presented with cardiac and thyroid abnormalities. These cases may suggest that the clinical phenotype of TNDM is more variable than previously believed. The contribution of genetic and epigenetic factors needs to be determined to elucidate the phenotype-genotype relationships of this disease.

show abstract

Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Variable features of transient neonatal diabetes mellitus with paternal isodisomy of chromosome 6

et al. 2000

View full text Add to dashboard Cite

show abstract

“…However, studies on cases with paternal isodisomy of chromosome 6 have demonstrated strong evidence that an imprinted gene linked to the HLA region is implicated in a mechanism of diabetes mellitus and an autoimmune disorder (Abramowicz et al 1994;Whiteford et al 1997;Arthur et al 1997;Temple et al 1995). This finding indicates that deregulation of genomic imprinting at the HLA-DQ region should have profound effects on pancreatic beta cell function and the immune system.…”

Section: Discussionmentioning

confidence: 99%

Preferential transmission of maternal allele with DQA10301-DQB10302 haplotype to affected offspring in families with type 1 diabetes

et al. 1999

View full text Add to dashboard Cite

To approach the possible involvement of an epigenetic mechanism in the pathogenesis of type 1 diabetes, we investigate here a parent-of-origin effect in transmission of the susceptible alleles at HLA-DQ loci by the transmission disequilibrium test. When we examined alleles of affected offspring of Japanese origin in 28 nuclear families, the maternal alleles were significantly different from the paternal alleles. Furthermore, the maternal alleles with the susceptible DQA1*0301-DQB1*0302 haplotype showed strong transmission disequilibrium with antiglutamic acid decarboxylase antibody-positive type 1 diabetes, while the paternal alleles with the same haplotype did not. This differential transmission disequilibrium of the susceptible allele was confirmed by the contingency table analysis for transmitted or nontransmitted alleles of both parental origin. The unique transmission of the susceptible allele observed supports the hypothesis that an epigenetic mechanism including genomic imprinting at the HLA-DQ region is involved in the pathogenesis and the genetic complexity of type 1 diabetes.

show abstract

“…A total of 5 further cases with TND and paternal UPD6 have since been reported in the literature (8)(9)(10)(11)(12), and another involved a child with diabetes who died at the age of 16 days (13). The association is now firmly established, although 2 cases of paternal UPD6 have been reported in older patients with no early history of TND, which cannot yet be explained (14,15).…”

mentioning

confidence: 99%

Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.

et al. 2000

View full text Add to dashboard Cite

Transient neonatal diabetes (TND) is a rare type of diabetes that presents soon after birth, resolves by 18 months, and predisposes to diabetes later in life. A total of 30 patients were ascertained and investigated for aberrations of chromosome 6. A genotype/phenotype study was also performed. Genotypically, these patients can be classified into 4 etiologic groups. Group 1 had paternal uniparental isodisomy of chromosome 6 (11 cases, including 1 set of identical twins). Group 2 had a duplication involving chromosome band 6q24, which was paternal in origin where tested (4 sporadic cases and 7 familial cases from 2 families). Group 3 consisted of 1 patient with a loss of methylation at a CpG island within the TND critical region (1 sporadic case). Group 4 had no identifiable rearrangement of chromosome 6 (7 sporadic cases). Most patients were growth retarded at birth, presented at a median age of 3 days, and recovered at a median age of 12 weeks. In group 2, 2 relatives of the TND patients who presented with type 2 diabetes and no early history of TND had inherited an identical duplication. An abnormality of chromosome 6 was identified in approximately 70% of sporadic TND cases and in all familial cases. No significant clinical differences were found between the 4 etiological groups. The study has broadened the clinical spectrum of TND to include type 2 diabetes presenting in later life with no neonatal presentation. The findings are consistent with an imprinted gene for diabetes mapping to 6q24, which we predict will have an important function in normal pancreatic development.

show abstract

Paternal uniparental disomy for chromosome 6 causes transient neonatal diabetes.

Cited by 44 publications

References 9 publications

Variable features of transient neonatal diabetes mellitus with paternal isodisomy of chromosome 6

Variable features of transient neonatal diabetes mellitus with paternal isodisomy of chromosome 6

Preferential transmission of maternal allele with DQA10301-DQB10302 haplotype to affected offspring in families with type 1 diabetes

Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.

Contact Info

Product

Resources

About

Paternal uniparental disomy for chromosome 6 causes transient neonatal diabetes.

Cited by 44 publications

References 9 publications

Variable features of transient neonatal diabetes mellitus with paternal isodisomy of chromosome 6

Variable features of transient neonatal diabetes mellitus with paternal isodisomy of chromosome 6

Preferential transmission of maternal allele with DQA1*0301-DQB1*0302 haplotype to affected offspring in families with type 1 diabetes

Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.

Contact Info

Product

Resources

About

Preferential transmission of maternal allele with DQA10301-DQB10302 haplotype to affected offspring in families with type 1 diabetes